1.Mechanism Study of Yinchenhao Tang Regulating Fas/Caspase-8/Caspase-3 Signaling Pathway to Improve Cholestatic Liver Injury
Zhengwang ZHU ; Linlin WANG ; Jinghan ZHAO ; Linjing SHE ; Yinpei TANG ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):39-46
ObjectiveTo explore the mechanism of Yinchenhao Tang regulating the tumor necrosis factor receptor superfamily member 6 (Fas)/cysteine protease-8 (Caspase-8)/cysteine protease-3 (Caspase-3) signaling pathway to inhibit hepatocyte apoptosis and improve cholestatic liver injury (CLI). MethodsAmong 48 Wistar rats,12 rats were randomly selected as the blank group,and the other rats were administered alpha-naphthalene isothiocyanate (ANIT) by gavage to induce a CLI model. The modeling rats were randomly divided into the model group, the ursodeoxycholic acid group(0.1 g·kg-1) and the Yinchenhao Tang group(9.23 g·kg-1),with 12 rats in each group. The rats in each group were given corresponding drugs by gavage for three consecutive days. The levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),gamma-glutamyl transpeptidase (γ-GT),total bilirubin (TBil) and total bile acid (TBA) in serum were detected. The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in liver tissue were detected. The histopathological changes of the liver were observed by hematoxylin-eosin (HE) staining. The protein and mRNA expressions of Fas,Caspase-8,Caspase-3,B-cell lymphoma-2 (Bcl-2) associated X protein (Bax) and Bcl-2 in liver tissue were detected by Western blot and real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with those in the blank group,the levels of ALT,AST,ALP,γ-GT,TBA and TBil in serum of the model group were significantly increased (P<0.01). The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly increased (P<0.01). The arrangement of hepatocytes was disordered,and inflammatory cell infiltration and bile duct epithelial cell proliferation were observed. The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly increased(P<0.05,P<0.01),while the protein and mRNA expressions of Bcl-2 were significantly decreased (P<0.05,P<0.01). Compared with those in the model group,the levels of ALP,γ-GT,TBA and TBil in the serum of rats in the ursodeoxycholic acid group were significantly decreased. The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased(P<0.05,P<0.01). The protein and mRNA expressions of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased (P<0.05,P<0.01),while the mRNA expression of Bcl-2 was significantly increased (P<0.05,). The levels of ALT,AST,γ-GT,TBA and TBil in the serum of rats in the Yinchenhao Tang group were significantly decreased (P<0.01). The levels and mRNA expressions of TNF-α and IL-1β in liver tissue were significantly decreased (P<0.05,P<0.01). The protein expression of Fas and Bax and the mRNA expression of Fas,Caspase-8,Caspase-3 and Bax in liver tissue were significantly decreased (P<0.05,P<0.01),while the protein and mRNA expression of Bcl-2 were significantly increased (P<0.05,P<0.01). Hepatocyte injury,inflammatory cell infiltration and proliferation of bile duct epithelial cells were reduced. ConclusionYinchenhao Tang can ameliorate CLI,and its mechanism may be related to inhibiting hepatocyte apoptosis mediated by the Fas/Caspase-8/Caspase-3 signaling pathway.
2.Mechanism of Yinchenhao Tang in Improving Cholestatic Liver Injury by Inhibiting TLR4/MyD88/NF-κB Signaling Pathway Through FXR
Zhengwang ZHU ; Yang YANG ; Jinghan ZHAO ; Linlin WANG ; Yinpei TANG ; Qingchun CAI ; Bing WANG ; Pingsheng ZHU ; Mingsan MIAO
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):47-54
ObjectiveTo study the mechanism of Yinchenhao Tang on the improvement of cholestatic liver injury (CLI) by inhibiting toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear transcription factor-κB (NF-κB) pathway via regulating farnesol X receptor (FXR). MethodsA total of 40 Wistar male rats were randomly selected, with 10 as a blank group,and the remaining rats were subjected to the CLI model induced by alpha-naphthalene isothiocyanate (ANIT). After modeling,they were randomly divided into the model group, the ursodeoxycholic acid (0.1 g·kg-1) group and the Yinchenhao Tang (9.23 g·kg-1) group,with 10 animals in each group. Each administration group was given the corresponding drug by intragastric administration for three consecutive days. Alanine aminotransferase (ALT),aspartate aminotransferase (AST),alkaline phosphatase (ALP),γ-glutamyl transpeptidase (γ-GT),total bile acid (TBA),total bilirubin (TBil) and direct bilirubin (DBil) levels in serum were detected. Tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),and interleukin-6 (IL-6) levels in liver tissue were detected. Real-time PCR was used to detect the mRNA expression of FXR,TLR4,MyD88,NF-κB,F4/80,TNF-α,IL-1β and IL-6 in liver tissue. Western blot was used to detect protein expression of FXR,TLR4,MyD88 and NF-κB in liver tissue. The histopathological changes of the liver were observed by hematoxylin-eosin (HE) staining. ResultsCompared with those in the blank group,ALT,AST,ALP,γ-GT,TBA,TBil and DBil levels in serum of rats in the model group were significantly increased (P<0.01). The levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were significantly increased (P<0.01),and the mRNA and protein expressions of FXR in liver tissue were decreased (P<0.01). The mRNA and protein expressions of TLR4,MyD88 and NF-κB and the mRNA expression of F4/80 were obviously increased (P<0.05,P<0.01). Hepatic histopathology showed inflammatory cell infiltration and proliferative changes of bile duct epithelial cells. Compared with those in the model group,ALT,ALP,γ-GT,TBA,TBil and DBil levels in serum of rats in the ursodeoxycholic acid group were obviously decreased (P<0.05,P<0.01),and the levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were obviously decreased (P<0.05,P<0.01). The mRNA and protein expressions of TLR4,MyD88 and NF-κB and the mRNA expression of F4/80 in liver tissue were obviously decreased (P<0.05,P<0.01). ALT,AST,ALP,γ-GT,TBA,TBil and DBil levels in the serum of rats in the Yinchenhao Tang group were obviously decreased (P<0.05,P<0.01),and the levels and mRNA expression of TNF-α,IL-1β and IL-6 in liver tissue were obviously decreased (P<0.01). The mRNA and protein expressions of FXR in liver tissue were significantly increased,and the mRNA expressions of TLR4,MyD88,NF-κB,and F4/80, as well as the protein expressions of TLR4 and NF-κB were obviously decreased (P<0.05,P<0.01). The inflammatory cell infiltration of liver tissue and the proliferation of bile duct epithelial cells decreased. ConclusionYinchenhao Tang has an obvious protective effect on CLI,and its mechanism may be related to regulating FXR to inhibit TLR4/MyD88/NF-κB pathway-mediated inflammatory response.
3.Congrong San alleviates hippocampal neuronal injury and ferroptosis in AD rats by inhibiting GRP78-PERK-ATF4 signaling pathway
Yuan-qin CAI ; Xian-bing CHEN ; Qing-hua LONG ; Xi WANG ; Zhen-ning WANG ; Chu-hua ZENG
Chinese Pharmacological Bulletin 2025;41(5):874-880
Aim To investigate the effects of Congrong San(CRS)on learning and memory ability,hippocam-pal neuronal injury,and ferroptosis in rats with Alzhei-mer's disease(AD)and to explore the related mecha-nisms.Methods AD rat models were established and divided into Sham,Model,CRS low-dose,CRS medium-dose,CRS high-dose,and memantine groups.After treatment,Morris water maze,HE and Nissl staining,transmission electron microscopy,immunofluorescence staining,Western blot,and kit assays were performed to assess learning and memory ability,hippocampal neuro-nal injury,ferroptosis-related indicatorsand glucose reg-ulated protein 78 ku(GRP78)-(proteinkinaseR-li-keERkinase)PERK-(activating transcription factor 4)ATF4 pathway protein expression.Results Com-pared with the model group,rats in the CRS medium-and high-dose groups and the memantine group showed significant improvement in learning and memory abili-ty,reduced hippocampal neuronal injury,increased number of Nissl bodies,and ameliorated endoplasmic reticulum swelling and mitochondrial damage.In addi-tion,the expressions of GRP78,p-PERK/PERK,and ATF4 were downregulated,while GPX4 expression was upregulated in the CRS medium-and high-dose groups and the memantine group.Moreover,MDA content de-creased,and SOD and GSH-PX levels increased in these groups.Conclusions CRS can improve the learning and memory ability in AD rats,reduce hipp-ocampal neuronal injury and ferroptosis,and its mecha-nism may be related to the inhibition of the GRP78-PERK-ATF4 pathway,enhancement of GPX4 expres-sion,and reduction of oxidative stress levels,providing a new approach for the clinical treatment of AD.
4.Study on the Deglycosylation Metabolism of Dioscin and Its Impact on the Proliferation of Human Colon Cancer Cells
Guoqiang ZHANG ; Zhenyao LU ; Huan WANG ; Bing HU ; Hong CAI
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(4):494-500
OBJECTIVE To investigate the deglycosylation metabolism of dioscin in vivo and the changes of its anti-tumor activi-ty of its deglycosylated metabolites.METHODS An LC-MS/MS analysis method for simultaneous determination of dioscin and its deglycosylation metabolites was established to study the cumulative excretion amount of dioscin and its deglycosylated metabolites in rat feces after oral administration.To mimic its deglycosylation metabolism,HPLC method was applied to investigate the time-dependent changes in the prototype components and metabolites of dioscin after incubation in artificial gastric juice.Solid-phase extraction tech-nology was employed to isolate the product of dioscin following hydrolysis by artificial gastric juice.The cytotoxic effects of this product on human colon cancer cells HCT-116 were assessed using the CCK-8 assay across different hydrolysis time periods.Concurrently,the enzymatic activities of caspase-3 and caspase-9,along with the expression levels of cytochrome C,were measured to elucidate the impact of dioscin post-hydrolysis on the cytotoxicity against HCT-116 cells.RESULTS Dioscin and its series of deglycosylated me-tabolites were detected in rat feces,revealing no significant differences in the cumulative excretion amounts of Polyphyllin Ⅴ and Pro-genin Ⅱ.Dioscin was shown to generate a range of deglycosylated metabolites in artificial gastric juice.Furthermore,dioscin and its deglycosylated metabolites inhibited the proliferation of HCT-116 cells,induced morphological changes,and increased the enzymatic activities of caspase-3 and caspase-9,as well as cytochrome C expression.However,it was observed that the antitumor activity of the deglycosylated metabolites diminished with prolonged hydrolysis time.CONCLUSION The deglycosylation metabolism of dioscin sig-nificantly attenuates its inhibitory effect on the proliferation of HCT-116 cells.Suppressing the acid-mediated or gut microbiota-medi-ated deglycosylation metabolism may be a promising strategy to preserve its antitumor activity.
5.Relationship between serum sST2 and cardiac diastolic function in elderly patients with coronary heart disease and chronic kidney disease
Huiying LI ; Bing ZHU ; Lili CAI ; Shen LIU ; Hongbin LIU ; Qiwei ZHU
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2025;27(3):270-273
Objective To investigate the relationship between serum soluble suppression of tumori-genicity 2(sST2)and cardiac diastolic function in elderly patients with coronary heart disease(CHD)and chronic kidney disease(CKD).Methods A total of 116 elderly CHD patients suffer-ing from CKD taking physical examinations at the Second Medical Center of Chinese PLA General Hospital from April 2021 to July 2022 were recruited,and according to their serum sST2 level,they were divided into high sST2 group(>28.65 μg/L,58 cases)and low sST2 group(≤28.65μg/L,58 cases).The baseline data of all subjected patients were collected,including N-terminal pro-B-type natriuretic peptide(NT-proBNP),as well as peak early diastolic mitral flow velocity(E),peak early diastolic mitral annular velocity(e'),isovolumetric relaxation time(IVRT)and some other indicators in echocardiography.Serum sST2 level was measured using chemilumines-cence assay.Pearson correlation analysis and multiple linear regression analysis were used for analysis.Results The high sST2 group had significantly larger proportion of diabetes and usingβ-blockers,higher levels of sST2,urea and logNT-proBNP,increased left ventricular mass index,thicker left ventricular posterior wall thickness,and elevated E/e'and IVRT,and lower levels of hemoglobin and triacylglycerol,and decreased e'value when compared with the low sST2 group(P<0.05,P<0.01).The correlation analysis showed that sST2 was positively correlated with taking β-blockers,urea and logNT-proBNP levels,and E/e'ratio(r=0.226,P=0.015;r=0.362,P=0.001;r=0.374,P=0.001;r=0.257,P=0.005),and negatively correlated with triglycerides,hemoglobin and e'value(r=-0.227,P=0.014;r=-0.314,P=0.001;r=-0.203,P=0.029).Multiple linear regression analysis displayed that sST2 was linearly correlated with triglycerides,urea and NT-proBNP levels,and E/e'(P<0.05,P<0.01).Conclusion Serum sST2 level is cor-related with cardiac diastolic function in elderly patients with comorbidities of CHD and CKD.
6.Chinese experts' consensus on principles of preoperative hair removal
Yiping MAO ; Jun ZHENG ; Lei LI ; Deyan YANG ; Bing ZHANG ; Lei YANG ; Wang JIA ; Peng KANG ; Hui JIAO ; Yun YANG ; Qi QI ; Shiqing FENG ; Xiao LONG ; Yuewei ZHANG ; Xiaohui WANG ; Lize WANG ; Yuan WEI ; Jichao ZHOU ; Minghui MAO ; Pengju XIN ; Hongyu TAN ; Dahong ZHANG ; Lianxin LIU ; Lei TAO ; Xietong WANG ; Xiaoning YUAN ; Mang CAI ; Li MU ; Fang DU ; Rongzhu CHEN ; Fengmao ZHAO ; Jiuzuo HUANG ; Mingzi ZHANG ; Jie ZHANG ; Baoguo WANG ; Kun WANG ; Fang LUO ; Jinhua ZHANG ; Nong HE ; Ling LYU ; Zhiyong ZONG
Chinese Journal of Nosocomiology 2025;35(10):1441-1449
To formulate an expert consensus on the principles of preoperative hair removal and provide scientific guidance for standardized removal of hair before surgical procedures so as to reduce the incidence of surgical site infections.METHODS Led by the Hospital Management Institute of National Health Commission of the People's Republic of China,this consensus was reached with the joint efforts from the expects of relevant fields such as surgeries,interventional therapies,nursing,and infection prevention and control.The consensus facilitates the classification and evaluation of literatures by following the evidence grade formulated by Oxford Evidence-based Medicine Center and focuses on the association of preoperative hair removal with surgical site infection,it reaches the evidence grade of expert consensus and recommendation intensity by integrating with discussions on meetings and clinical experience of the expects from relevant fields.RESULTS A total of 6 items of consensus were reached by summarizing the latest evidence on the aspects including the indications for preoperative hair removal,tools,range,timing and places.CONCLUSION The consensus,to some extent,make supplements to and complete the exiting regulations and standards.It provides guidance for the medical institutions to carry out the preoperative hair removal.
7.Establishment and validation of urine AD7c-NTP reference intervals for healthy adults in Mianyang area using the indirect method
Yurong ZHANG ; Yifei HE ; Ping YANG ; Zixi XU ; Zhilong CAI ; Yang LIU ; Dan WANG ; Liang HUANG ; Bing HOU ; Jia YANG ; Xuemei JIANG ; Kun FANG
Chinese Journal of Clinical Laboratory Science 2025;43(5):378-381
Objective To establish the reference interval of urine Alzheimer-associated neuronal thread protein(AD7c-NTP)for healthy adults in Mianyang area using the indirect method.Methods The detection results of urine AD7c-NTP from 5 093 healthy in-dividuals were collected from the information management database of Medical Laboratory Department of Sichuan Science City Hospital from March 2017 to March 2022.Skewness-kurtosis and Kolmogorov-Smirnov tests were used to determine whether the data followed a normal distribution.After removing outliers using the Box Plots method,the enrolled subjects were grouped by gender and age.The Mann-Whitney U or Kruska-Wallis H tests were used to analyze the between-group differences of urine AD7c-NTP in healthy individu-als with different genders and ages.The adjacent age groups without statistically significant difference(P>0.05)were combined,and the indirect method(non-parametric test method)was used to calculate the reference intervals for different gender and age groups.Results Skewness-kurtosis and Kolmogorov-Smirnov tests showed that the data followed a non-normal distribution.After removing 293 outliers using the Box Plots method,a total of 4 800 subjects,including 3 199 males and 1 601 females,were enrolled.The enrolled subjects were grouped by gender and age,and the non-parametric test method were used to establish the reference intervals of urine AD7c-NTP in healthy populations with different genders.The Mann-Whitney U test confirmed that urine AD7c-NTP levels existed gen-der differences(Z=14.09,P<0.01),and the reference intervals for males and females were≤1.10 ng/mL and≤1.40 ng/mL,re-spectively.There were also statistical differences in urine AD7c-NTP levels among different age groups of the same gender.After combi-ning adjacent age groups without statistically significant difference(P>0.05),the reference intervals of urine AD7c-NTP in healthy populations with different genders and ages were established by the non-parametric test method,which were≤1.00 ng/mL for male 20-39 years old group,≤1.10 ng/mL for male 40-79 years old group,≤1.60 ng/mL for male≥80 years old group,≤1.30 ng/mL for female 20-69 years old group,and≤1.60 ng/mL for female≥70 years old group,respectively.The established reference intervals of urine AD7c-NTP were further verified by healthy individuals,and the results met the standards.Conclusion The reference intervals of urine AD7c-NTP in healthy populations with different genders and ages in Mianyang area are established successfully using the indi-rect method,which may help to predict the risk of Alzheimer's disease in clinical practice and provide support for the diagnosis and treatment of the disease.
8.Genetic evolution analysis of enteric cytopathogenic human orphan virus type 30 in three cases of infants and young children in Hubei Province
Kangping ZHOU ; Bing HU ; Kai PAN ; Kun CAI
Chinese Journal of Preventive Medicine 2025;59(1):95-100
Three throat swab samples from infants and young children in Hubei Province were identified as positive for enteroviruses. All subjects were one month old, and the onset of symptoms occurred in June; these cases were sporadic and exhibited no clear epidemiological associations. The results of VP1 gene amplification analysis indicated that all three infant cases were attributed to Echovirus 30 (ECHO30). The ECHO30 strain isolated from the three samples was classified as Cluster Ⅲ within the H gene subtype. Whole genome amplification analysis revealed that the ECHO30 strain from Hubei exhibited the highest homology with ECHO30/MW586892/Ashburton/17WQ2027G/USA/2007-08-20 from GenBank, demonstrating nucleotide and amino acid homologies of 97.6% and 99.3%, respectively. Recombination analysis indicated the presence of recombination events in the non-structural protein region of the ECHO30 Hubei strain, with recombinant fragments potentially originating from ECHO30/KY888274/14-397/Germany/2013 and ECHO18 strains Echo18/MN815811/BJ2018-S6363/Beijing/2018. This study provides a comprehensive analysis of the genetic evolution of the ECHO30 strain prevalent in Hubei Province, contributing essential data for the prevention of ECHO30 infections.
9.Congrong San alleviates hippocampal neuronal injury and ferroptosis in AD rats by inhibiting GRP78-PERK-ATF4 signaling pathway
Yuan-qin CAI ; Xian-bing CHEN ; Qing-hua LONG ; Xi WANG ; Zhen-ning WANG ; Chu-hua ZENG
Chinese Pharmacological Bulletin 2025;41(5):874-880
Aim To investigate the effects of Congrong San(CRS)on learning and memory ability,hippocam-pal neuronal injury,and ferroptosis in rats with Alzhei-mer's disease(AD)and to explore the related mecha-nisms.Methods AD rat models were established and divided into Sham,Model,CRS low-dose,CRS medium-dose,CRS high-dose,and memantine groups.After treatment,Morris water maze,HE and Nissl staining,transmission electron microscopy,immunofluorescence staining,Western blot,and kit assays were performed to assess learning and memory ability,hippocampal neuro-nal injury,ferroptosis-related indicatorsand glucose reg-ulated protein 78 ku(GRP78)-(proteinkinaseR-li-keERkinase)PERK-(activating transcription factor 4)ATF4 pathway protein expression.Results Com-pared with the model group,rats in the CRS medium-and high-dose groups and the memantine group showed significant improvement in learning and memory abili-ty,reduced hippocampal neuronal injury,increased number of Nissl bodies,and ameliorated endoplasmic reticulum swelling and mitochondrial damage.In addi-tion,the expressions of GRP78,p-PERK/PERK,and ATF4 were downregulated,while GPX4 expression was upregulated in the CRS medium-and high-dose groups and the memantine group.Moreover,MDA content de-creased,and SOD and GSH-PX levels increased in these groups.Conclusions CRS can improve the learning and memory ability in AD rats,reduce hipp-ocampal neuronal injury and ferroptosis,and its mecha-nism may be related to the inhibition of the GRP78-PERK-ATF4 pathway,enhancement of GPX4 expres-sion,and reduction of oxidative stress levels,providing a new approach for the clinical treatment of AD.
10.Study on the ultrasonic cleaning effect and influencing factors of emergency laparoscopic surgical instruments at night
Bing-jie SUN ; Yu-qing CAI ; Gao-feng YUAN ; Ju-hua WU
Journal of Regional Anatomy and Operative Surgery 2025;34(2):121-124
Objective To explore the ultrasonic cleaning effect and influencing factors of emergency laparoscopic surgical instruments at night.Methods A total of 698 emergency laparoscopic surgical instruments cleaned by ultrasound at night were selected as the research subjects,and the unqualified ultrasonic cleaning of instruments was statistically analyzed.Univariate and multivariate binary Logistic regression equations were used to analyze the factors that may lead to unqualified ultrasonic cleaning.Results Among 698 ultrasonic cleaning sessions for emergency laparoscopic surgical instruments at night,a total of 55 times(7.88%)were unqualified.The results of univariate and multivariate binary Logistic regression analysis showed that the time from cleaning to the end of surgery≥10 hours,luminal surgical instruments,nonstandard pretreatment,unqualified cleaning water quality,and unqualified cleaning medium were the risk factors that lead to the occurrence of unqualified ultrasonic cleaning of emergency laparoscopic surgical instruments at night(OR>1,P<0.05),while manual+ultrasonic cleaning was the protective factor to avoid the occurrence of unqualified ultrasonic cleaning of emergency laparoscopic surgical instruments at night(OR<1,P<0.05).Conclusion The unqualified rate of ultrasonic cleaning of emergency laparoscopic surgical instruments at night is relatively high,so it should be cleaned as early as possible after the surgery.Before ultrasonic cleaning,manual clean-ing should be carried out as much as possible,especially for luminal surgical instruments that are difficult to clean,standardized pretreatment should be carried out,and qualified cleaning water quality and medium should be selected.

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